It turns out to be a lot easier than assumed. And that is very good news!
Our bones are indispensable in our body. They are the scaffolding material for muscles through which we can move and protect vulnerable organs such as our brains and lungs. In addition, they house stem cells that produce our blood and immune system. Researchers have now shown in a new study that the way bones form takes place very differently than previously thought. And that is hopeful news for the future.
Complexe biomoleculen
Bones consist mainly of a mix of collagen (long strands of connective tissue) and tiny crystals of calcium phosphate. “Nothing was known about exactly how the crystals in that collagen grow into small plates and group themselves in roof tiles,” says Nico Sommerdijk, biochemical researcher at Radboudumc. “The generally accepted idea was that bioactive molecules of that collagen string the crystals together to form plates 3 nanometers thick, 20 nanometers wide and 65 nanometers long.”
Doubt
For a long time it was thought that complex biomolecules in collagen are needed for the formation of bones. But Sommerdijk doubted that. “When we replaced the calcium phosphate with other minerals, the same tiny images were created,” he says. “Bioactive molecules are very selective, which immediately made us question that predominant idea.” On such a tiny scale, however, the processes could not be clearly visualized about a decade ago. But that has changed in the meantime. The researcher decided to start a study against the established order. And now, ten years later, that decides in his favor.
The process of how bones grow cannot be followed closely. Sommerdijk therefore used a model to simulate bone growth outside an organism, which reveals the process step by step. The model turns out to be very accurate. Because the end result is comparable to what is found in human bone material that sometimes becomes available after surgery. Step by step, the researchers have thus provided new underpinnings of the way our bone is formed, how it grows and hardens.
Stacked playing cards
The first thing Sommerdijk undermines is the stacking of the crystallized pictures ‘like playing cards in a box’. The researcher made approximately one hundred two-dimensional images of bone at different angles with the help of an electron microscope. He then converted this into three-dimensional images. And that leads to an interesting conclusion. The pictures are all in the longitudinal direction of the collagen, but certainly not like neatly stacked playing cards against each other. There are always pictures to be seen, which lie against each other at different angles.
Organization of mineral crystals in bone. A) The old model with all crystals as “playing cards in a box”. B & C) Electron microscope images of the bone crystals in the collagen with B) in the longitudinal direction and C) in the transverse direction, D) the new model with the crystals aligned only in the longitudinal direction. Image: Radboudumc
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Next, the researcher examined the function of the collagen. Collagen appears to have thin longitudinal cavities, into which calcium phosphate enters and starts to crystallize. “That does not happen under the guidance of bioactive molecules in the collagen,” says Sommerdijk. “It is a blind process dominated by the laws of physical chemistry. Calcium phosphate that crystallizes in the longitudinal direction has – precisely because of those thin collagen cavities – a selection advantage. As a result, initially only very thin needles are formed in such a cavity. The needle then grows into a small plate of calcium phosphate, which pushes away the surrounding collagen. ”
Bone substitutes and biomaterials
The study shows that the way bone formation takes place needs to be rewritten. Because the findings show that no complex biomolecules in collagen are needed at all. Moreover, this discovery also has consequences for practice. Because this makes the production of bone substitutes and biomaterials a lot easier than expected. “If the growth of crystals does not have to take place in a matrix with very complex and expensive biomolecules, but it can also simply be done in channels of cheap polymer, then making biomaterials and bone substitutes will be a lot easier,” says cell biologist Anat Akiva. . “We don’t have to sacrifice the properties of these materials. And that makes our finding important for the patient. ”
The results, published in the prestigious magazine Nature Communications, change our view of how bones are formed. But this does not reveal all the secrets about bone formation. “Bone is not only formed inside, but also outside the collagen,” says Sommerdijk. “Various proteins seem to play a role there.” With an ERC advanced grant of 3.5 million euros that he previously received, he is now also trying to gain more insight into this.
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